New Study Questions the Effectiveness of Tramadol in Chronic Pain Management

Asian Pain Academy
11 hours ago
4 min read

Updated: 6 minutes ago

Introduction

Tramadol has long been regarded as a “safer opioid,” often prescribed for the management of chronic non-cancer pain. Its dual mechanism — weak μ-opioid receptor agonism and inhibition of serotonin and norepinephrine reuptake — made it a preferred choice for clinicians seeking an alternative to stronger opioids.

However, a new systematic review and meta-analysis published in BMJ Evidence-Based Medicine (2025) has raised Important questions about tramadol’s true effectiveness and safety profile in chronic pain management. Conducted by Jehad Ahmad Barakji and colleagues, this large-scale analysis brings into focus the delicate balance between modest pain relief and significant adverse outcomes associated with long-term tramadol use.

About the Study on Tramadol in chronic pain Management

Title: Tramadol versus placebo for chronic pain: a systematic review with meta-analysis and trial sequential analysis

Published in: BMJ Evidence-Based Medicine, 2025

Authors: Barakji JA, Maagaard M, Petersen JJ, Ipsen EØ, Mathiesen O, Jakobsen JC, et al.

DOI: 10.1136/bmjebm-2025-114101

Study Objective

To evaluate the benefits and harms of tramadol compared with placebo in adults with chronic pain, regardless of pain type or origin.

Methodology

Design: Systematic review and meta-analysis of randomized clinical trials
Number of studies included: 19 placebo-controlled trials
Total participants: 6,506 adults
Databases searched: Cochrane Library, MEDLINE, Embase, Science Citation Index, BIOSIS (up to Feb 2025)
Quality assessment: Conducted using the Cochrane Risk of Bias Tool and the GRADE approach
Statistical tools: Trial Sequential Analysis (TSA) and Beta-binomial regression

Findings

1. Pain Reduction Was Minimal

Tramadol showed a statistically significant reduction in pain scores compared to placebo (mean difference: −0.93 points on a 0–10 numerical rating scale).
However, the reduction was below the predefined minimal clinically Important difference (MCID) of 1 point — meaning the improvement was not meaningful to most patients in real-life settings.
Evidence certainty: Low.

2. Increased Risk of Serious Adverse Events

Patients taking tramadol had more than twice the risk of serious adverse events compared with placebo (Odds Ratio: 2.13; 97.5% CI 1.29–3.51).
The most frequent serious events were cardiac complications and neoplasms.
Evidence certainty: Moderate.

3. Common Non-Serious Adverse Events

Tramadol significantly increased the incidence of several non-serious but clinically bothersome side effects:

Nausea (Number Needed to Harm = 7)
Dizziness (NNH = 8)
Constipation (NNH = 9)
Somnolence (NNH = 13)
Evidence certainty: Very low.

4. Lack of Evidence for Quality of Life Improvement

The review found no conclusive data to support improvement in quality of life or function with tramadol use.
Several included trials failed to report these outcomes or had high risk of bias.

5. Dependence and Abuse Potential

Although tramadol is a Schedule H1 drug in India and considered to have lower abuse potential than stronger opioids, the study emphasized its risk for dependence and withdrawal, especially in long-term users.

Interpretation of Findings

The findings suggest that tramadol provides only minimal pain relief, which may not translate to a noticeable improvement in patients’ daily function or quality of life. At the same time, the increased risk of serious and minor adverse effects raises legitimate safety concerns.

These results challenge the perception of tramadol as a “safe and effective” long-term analgesic and call for careful patient selection and close monitoring when it is prescribed for chronic pain conditions.

Clinical Implications for Pain Practitioners

1. Reassessing the Role of Tramadol

Tramadol may still have a role in short-term management of moderate acute pain (e.g., post-operative or injury-related pain), but its long-term use in chronic non-cancer pain appears unjustified based on this evidence.

2. Risk–Benefit Assessment

Before initiating tramadol, clinicians should:

Evaluate the severity and chronicity of pain
Consider non-opioid alternatives and multimodal strategies
Counsel patients on potential adverse events and dependency risks

3. Emphasizing Non-Opioid and Interventional Approaches

Evidence-based non-opioid alternatives include:

NSAIDs, duloxetine, pregabalin (for neuropathic pain)
Physical therapy and rehabilitation
Interventional pain procedures, such as nerve blocks, radiofrequency ablation, or neuromodulation

These approaches can provide sustained pain relief without opioid-related complications.

The Role of Education in Responsible Pain Management

As this study demonstrates, the evidence for long-term pharmacological therapy in chronic pain is limited. Pain physicians must remain updated on evolving evidence to ensure rational prescribing and prioritize safer, effective methods.

At the Asian Pain Academy, we integrate pharmacological evidence review with hands-on training in interventional and ultrasound-guided procedures. Our aim is to reduce dependency on long-term analgesics and promote precision-guided, mechanism-based pain management.

Conclusion

This 2025 meta-analysis concludes that tramadol provides limited benefit and potentially significant harm in chronic pain management. While it remains a useful option for short-term analgesia, clinicians should exercise caution when prescribing it for persistent pain conditions.

The balance between minimal analgesic gain and considerable risk makes tramadol less favorable as a first-line option for chronic pain.

Pain physicians are encouraged to adopt a multimodal, individualized approach, integrating interventional techniques, rehabilitation, and patient education — rather than relying solely on opioids for long-term symptom control.

Asian Pain Academy